The Impact of Varied Durations of Sleep Deprivation on Anxiety and Depressive-like Behaviors in Mice

Abstract Sleep disorders and depression often coexist, and preclinical studies using animal models are crucial for improving the treatment of depression. However, previous studies have not compared the effects of different durations of sleep deprivation on depression, nor have they explored the optimal time period for treatment following sleep deprivation. In our study, we aimed to investigate the mechanisms through which sleep deprivation induces anxiety- and depression-like behaviors in mice and determine the most effective timeframe for treatment. Additionally, we briefly examined the relationship between inflammation and the pathophysiology of depression. To create a model of depression, we utilized adult male C57BL/6J mice and subjected them to sleep deprivation. Following the sleep deprivation period, the mice were allowed to sleep normally for either 14 or 21 days. We employed five behavioral tests to assess anxiety and depression-like behaviors. Furthermore, we conducted H&E staining and Nissl staining to examine cell morphology and neuronal changes. Real-time fluorescence quantitative PCR (RT-qPCR) was employed to measure mRNA levels of clock genes, Silent information regulator 6 (Sirt6), High mobility group box-1 (Hmgb1) , and inflammatory factors. Our study demonstrates that sleep deprivation serves as a reliable mouse model for depression, with 7 or 14 days of sleep deprivation considered optimal. Moreover, the recommended duration for effectively treating sleep deprivation-induced depression in animal models is 14 days. Limited evidence suggests that sleep deprivation may impact the Sirt6/Hmgb1 pathway and influence the transcription of clock genes, thereby activating inflammation in the medial prefrontal cortex (mPFC) region of mice.